The objective is to continue investigations of the mechanisms which underlie (a) the maintenance of immunologic self-tolerance and (b) the induction of autoimmunity, employing experimental allertic encephalomyelitis (EAE) as a model system. Studies will include further characterization of suppressor cells which function in the maintenance of unresponsiveness to EAE, by means of adoptive transfer of different populations oflymphocytes to syngeneic recipient rats, and the mechanism through which they function. We will also continue the functional dissection of the myelin basic protein antigen (BP) in an attempt to further identify determinants involved in the induction of (a) EAE, (b) unresponsiveness to EAE, and (c) cell-mediated immunity to BP, as an approach to elucidating the immunochemical requirements of the autoimmune response with respect to interaction between antigenic determinants and lymphocytes. We will initiate experiments directed toward identifying the effector mechanisms involved in the pathogenesis of EAE. In vitro cytotoxicity studies will be employed in order to determine whether T-lymphocyte-mediated, or antibody-dependent cytotoxicity can be correlated with EAE. These studies offer promise with respect to understanding the pathogenesis of human demyelinating diseases like multiple sclerosis.